Communication of gut hormones with the central nervous system is important to regulate systemic glucose homeostasis, but the precise underlying mechanism involved remain little understood. Nesfatin-1, Show more
Communication of gut hormones with the central nervous system is important to regulate systemic glucose homeostasis, but the precise underlying mechanism involved remain little understood. Nesfatin-1, encoded by nucleobindin-2 (NUCB2), a potent anorexigenic peptide hormone, was found to be released from the gastrointestinal tract, but its specific function in this context remains unclear. Herein, we found that gut nesfatin-1 can sense nutrients such as glucose and lipids and subsequently decreases hepatic glucose production. Nesfatin-1 infusion in the small intestine of NUCB2-knockout rats reduced hepatic glucose production via a gut - brain - liver circuit. Mechanistically, NUCB2/nesfatin-1 interacted directly with melanocortin 4 receptor (MC4R) through its H-F-R domain and increased cyclic adenosine monophosphate (cAMP) levels and glucagon-like peptide 1 (GLP-1) secretion in the intestinal epithelium, thus inhibiting hepatic glucose production. The intestinal nesfatin-1 -MC4R-cAMP-GLP-1 pathway and systemic gut-brain communication are required for nesfatin-1 - mediated regulation of liver energy metabolism. These findings reveal a novel mechanism of hepatic glucose production control by gut hormones through the central nervous system. Show less
Cellular senescence is a hallmark for cancers, particularly in lung adenocarcinoma (LUAD). This study developed a risk model using senescence signature genes for LUAD patients. Based on the RNA-seq, c Show more
Cellular senescence is a hallmark for cancers, particularly in lung adenocarcinoma (LUAD). This study developed a risk model using senescence signature genes for LUAD patients. Based on the RNA-seq, clinical information and mutation data of LUAD patients collected from the TCGA and GEO database, we obtained 102 endotheliocyte senescence-related genes. The "ConsensusClusterPlus" R package was employed for unsupervised cluster analysis, and the "limma" was used for the differentially expressed gene (DEG) analysis. A prognosis model was created by univariate and multivariate Cox regression analysis combined with Lasso regression utilizing the "survival" and "glmnet" packages. KM survival and receiver operator characteristic curve analyses were conducted applying the "survival" and "timeROC" packages. "MCPcounter" package was used for immune infiltration analysis. Immunotherapy response analysis was performed based on the IMvigor210 and GSE78220 cohort, and drug sensitivity was predicted by the "pRRophetic" package. Cell invasion and migration were tested by carrying out Transwell and wound healing assays. According to the results, a total of 32 genes related to endotheliocyte senescence were screened to assign patients into C1 and C2 subtypes. The C2 subtype showed a significantly worse prognosis and an overall higher somatic mutation frequency, which was associated with increased activation of cancer pathways, including Myc_targets2 and angiogenesis. Then, based on the DEGs between the two subtypes, we constructed a five-gene RiskScore model with a strong classification effectiveness for short- and long-term OS prediction. High- and low-risk groups of LUAD patients were classified by the RiskScore. High-risk patients, characterized by lower immune infiltration, had poorer outcomes in both training and validation datasets. The RiskScore was associated with the immunotherapy response in LUAD. Finally, we found that potential drugs such as Cisplatin can benefit high-risk LUAD patients. In-vitro experiments demonstrated that silencing of Angiopoietin-like 4 (ANGPTL4), Gap Junction Protein Beta 3 (GJB3), Family with sequence similarity 83-member A (FAM83A), and Anillin (ANLN) reduced the number of invasive cells and the wound healing rate, while silencing of solute carrier family 34 member 2 (SLC34A2) had the opposite effect. This study, collectively speaking, developed a prognosis model with senescence signature genes to facilitate the diagnosis and treatment of LUAD. Show less
SANET-ep (NCT02588170) and SANET-p (NCT02589821) demonstrated the efficacy and safety of surufatinib versus placebo in patients with advanced extra-pancreatic and pancreatic neuroendocrine tumours (NE Show more
SANET-ep (NCT02588170) and SANET-p (NCT02589821) demonstrated the efficacy and safety of surufatinib versus placebo in patients with advanced extra-pancreatic and pancreatic neuroendocrine tumours (NETs). Here, we present a pooled analysis of final overall survival (OS) from two randomised phase 3 studies. The SANET studies were randomised, placebo-controlled, double-blind, phase 3 studies in China, comparing the efficacy and safety of oral 300-mg surufatinib (nβ―=β―265) versus placebo (nβ―=β―133) in patients with unresectable/metastatic, well-differentiated NETs (grade 1/2). After progression of disease or study unblinding, patients receiving placebo crossed over/switched to open-label surufatinib. By pooling the data from the two studies, OS analysis was completed using Kaplan-Meier methodology and a Cox proportional hazards model in the intention-to-treat population. Exploratory analyses were performed using different models to correct the confounding effect introduced by crossover. Long-term safety was assessed. At study termination, 69 % of the placebo group had crossed over/switched to surufatinib. Median OS was 50.1 versus 46.8 months for patients initially on surufatinib versus those initially on placebo (stratified hazard ratio [HR] 0.935, 95 % confidence interval [CI] 0.684-1.278; pβ―=β―0.6727). After correcting the confounding effect introduced by crossover/switching, the HR ranged from 0.558 to 0.825. Commonly (β₯10 %) reported treatment-related adverse events (grade 3/4) included hypertension and proteinuria. OS of patients initially on surufatinib was not significantly longer versus patients initially on placebo, likely due to the high amount of crossover from placebo to surufatinib. No new safety signals were observed. SANET-ep (NCT02588170) and SANET-p (NCT02589821). Show less
Liver X receptor Ξ± (LXRΞ±) plays an important role in inflammatory immune response induced by hepatic ischemia-reperfusion injury (IRI) and acute rejection (AR). Macrophage M1-polarization play an impo Show more
Liver X receptor Ξ± (LXRΞ±) plays an important role in inflammatory immune response induced by hepatic ischemia-reperfusion injury (IRI) and acute rejection (AR). Macrophage M1-polarization play an important role in the occurrence and development of AR. Although the activation of LXR has anti-inflammatory effects, the role of LXRΞ± in AR after liver transplantation (LT) has not been elucidated. We aimed to investigate LXRΞ± anti-inflammatory and macrophage polarization regulation effects and mechanisms in acute rejection rat models. LXRΞ± anti-inflammatory and liver function protective effects was initially measured in primary Kupffer cells and LT rat models. Subsequently, a flow cytometry assay was used to detect the regulation effect of LXRΞ± in macrophage polarization. HE staining, TUNEL and ELISA were used to evaluate the co-treatment effects of TO901317 and tacrolimus on hepatic apoptosis and liver acute rejection after LT. In this study, we found that LPS can inhibit the expression of LXRΞ± and activate MAPK pathway and PI3K/AKT/mTOR. We also found that LXRΞ± agonist (TO901317) could improve liver function and rat survival after LT by activating the level of ABCA1 and inhibiting MAPK. TO901317 could inhibit macrophage M1-polarization by activating PI3K/AKT/mTOR signal pathway to improve the liver lesion of AR rats after liver transplantation. Additionally, co-treatment with TO901317 and tacrolimus more effectively alleviated the damaging effects of AR following LT than either drug alone. Our results suggest that the activation of LXRΞ± can improve liver function and rat survival after LT by regulate ABCA1/MAPK and PI3K/AKT/mTOR signaling axis in macrophages. Show less
To clarify the anatomical characteristics of the lateral plantar ligament (LPL) of the transverse metatarsal arch (TMA) in the population of southwest Shandong Province, so as to complement the anatom Show more
To clarify the anatomical characteristics of the lateral plantar ligament (LPL) of the transverse metatarsal arch (TMA) in the population of southwest Shandong Province, so as to complement the anatomical structures of the midfoot and Lisfranc joint complexes. A total of 100 adult lower limbs were dissected and the types of LPL were divided according to their insertions, among them, 63 were (63%) and 37 were female (37%); 50 were on the left side (50%) and 50 were on the right side (50%). The fiber bundle length, origin width, insertion width, and thickness of the LPL were measured. (1) According to the insertions of the LPL, they were divided into: β Type I, the LPL was inserted at the base of the second metatarsal (M2) in 47 cases; β‘ Type II, the LPL was inserted at the base of M2 and fused with tibialis posterior tendon (TPT) in 16 cases; β’ Type III, the LPL was absent in 16 cases; β£ Type IV, the LPL was inserted at TPT in 6 cases; β€ Type V, the LPL was inserted at the intermediate cuneiform (IC) in 1 case; β₯ Type VI, bifid LPL with one bundle inserted at the base of M2, and the other bundle inserted at the medial cuneiform (MC) in 4 cases; β¦ Type VII, two bundles of LPL inserted at the base of M2 in 8 cases; β§ Type VIII, the LPL consisted of 3 bundles; the distal, middle and proximal bundles was inserted at the base of M2, the TPT and the lateral side of navicular bone in 2 cases, respectively. (2) There was a statistical significance in the length of LPL between male (31.62βΒ±β3.83) mm and female (28.07βΒ±β3.46) mm (t=-3.050, Pβ=β0.003). There was no statistical significance in the types of LPL between male and female (Z=-1.721, Pβ>β0.05), and no statistical significance in the types between left and right sides (Z=-0.026, Pβ>β0.05). According to our research, LPL originates from M5 and is divided into 8 types according to its insertion location, of which insertion at the base of M2 is the most common. In addition, we found that LPL has fibrous fusion with the long plantar ligament and the TPT, which may be involved in maintaining arch stability. The classification of LPL in this study is a supplement to the anatomical structure of the middle foot and Lisfranc joint complex, providing a new direction for the diagnosis and treatment of middle foot and arch injury in the future. Show less
Amyloid transthyretin (ATTR) amyloidosis is a rare, life-threatening disease frequently manifesting with cardiomyopathy (ATTR-CM), polyneuropathy (ATTR-PN) or both (ATTR-mixed). We retrospectively ana Show more
Amyloid transthyretin (ATTR) amyloidosis is a rare, life-threatening disease frequently manifesting with cardiomyopathy (ATTR-CM), polyneuropathy (ATTR-PN) or both (ATTR-mixed). We retrospectively analysed US electronic health records and claims data to provide up-to-date estimates of ATTR amyloidosis epidemiology (overall and by phenotype). Data were extracted from the Clarivate Real-World Data repository (2016-2023). Given the lack of established coding for ATTR amyloidosis, we used different combinations of diagnostic codes to obtain narrow and broad estimates of incident and prevalent cases in the USA in 2022. Temporal trends (2019-2022) were also assessed. Using narrow definitions, the 2022 estimated incidence of ATTR amyloidosis overall, ATTR-CM, ATTR-PN and ATTR-mixed was 16.6, 12.7, 3.5 and 1.9 cases per million people, respectively; the corresponding prevalence estimates were 59.8, 41.1, 15.1 and 9.8 cases per million people. Estimates were consistently lower with the narrow (vs broad) definitions. Over time, the incidence and prevalence of ATTR amyloidosis overall increased, driven by ATTR-CM cases. No major changes were reported for the other phenotypes. This study provides comprehensive and up-to-date epidemiological data for ATTR amyloidosis in the USA. Our findings corroborate the need for appropriate differential diagnostic coding and standardised criteria. Show less
To investigate the influence of MEK5/ERK5 pathway on mitophagy in osteosarcoma (OS), as well as the involved molecular mechanisms. The overlapped genes of mitophagy-related genes from MSigDB database Show more
To investigate the influence of MEK5/ERK5 pathway on mitophagy in osteosarcoma (OS), as well as the involved molecular mechanisms. The overlapped genes of mitophagy-related genes from MSigDB database and DEGs between metastatic and primary OS groups from GSE32981 were identified. GSVA of mitophagy-related pathways between the metastatic and primary groups were analyzed. The relationships between Nur77 and mitophagy-related pathways, prognosis, immune infiltrating cells, immune response gene sets were investigated. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting were utilized to assess the expression levels of MEK5, ERK5, Nur77, PINK1, and Parkin. Cellular behaviors and mitochondrial potential were evaluated via CCK-8, Transwell assay and JC-1 staining. Total 4 overlapped genes were obtained as mitophagy-related DEGs, including GABARAPL1, HIF1A, PINK1, and RB1CC1. The activity scores of 3 mitophagy-related pathways exhibited significant differences between metastatic and primary groups. Importantly, Nur77 was significantly negatively correlated with a mitophagy-related pathway (GOBP MITOPHAGY: Rβ=β-Β 0.48, Pβ=β0.02). The Nur77 expression in metastatic group was remarkedly higher than that in the primary group (Pβ<β0.001). Patients with high Nur77 expression had poor prognosis, with AUC values all above 0.615 in predicting 1-, 3-, and 5-year survival. In addition, Nur77 was closely related to numerous immune cells, including activated dendritic cells, activated mast cells and M0 macrophages, and immune response gene sets chemokines and cytokines (all Pβ<β0.05). In addition, MEK5/ERK5 pathway is activated in OS, and Nur77 is overexpressed in OS, and MEK5/ERK pathway promotes Nur77 expression, tumorigenesis and mitochondrial function in U2OS cells. Cytosporone B implement significantly increased the tumorigenesis of U2OS cells in sh-MEK5 group, and inhibited the weaken in mitochondrial membrane potential caused by MEK5 downregulation, and reversed the protein levels of mitophagy markers PINK1 and Parkin in sh-MEK5 group. MEK5-ERK5 pathway mediates mitophagy by regulating Nur77 to promote tumorigenesis of OS cells. These findings offered promising therapeutic targets for OS. Show less
Tafolecimab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), represents a significant therapeutic advancement in the management of hypercholesterolem Show more
Tafolecimab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), represents a significant therapeutic advancement in the management of hypercholesterolemia and has been approved for use in the Chinese population. Elevated low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerotic cardiovascular disease, and traditional treatments often fall short due to challenges such as statin intolerance. Clinical trials have demonstrated that tafolecimab can effectively reduce LDL-C levels, achieving reductions of over 60% in many patients. It also improves other lipid parameters, including lipoprotein(a) [Lp(a)], non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (ApoB). It has a favorable safety profile, primarily characterized by mild to moderate adverse events. The long-acting formulation of tafolecimab enables less frequent dosing, thereby promoting compliance. As cardiovascular diseases continue to escalate globally, tafolecimab holds promise not only for patients in China but also for broader international applications, representing a critical advancement in the evolving landscape of lipid-lowering therapies. Show less
Growing evidence indicates that healthy diets are associated with a slower progression of Alzheimer's disease (AD). Flavonoids are among the most abundant natural products in diets beneficial to AD, s Show more
Growing evidence indicates that healthy diets are associated with a slower progression of Alzheimer's disease (AD). Flavonoids are among the most abundant natural products in diets beneficial to AD, such as the Mediterranean diet. However, the effect and mechanism of these dietary flavonoids on AD remains incompletely understood. Here, we found that a representative dietary natural flavonoid, chrysin (Chr), significantly ameliorated cognitive impairment and AD pathology in APP/PS1 mice. Furthermore, mechanistic studies showed that Chr significantly reduced the levels of amyloid-Ξ² (AΞ²) and phosphorylated tau (p-tau), along with dual inhibitory activity against Ξ²-site amyloid precursor protein cleaving enzyme 1 (BACE1) and glycogen synthase kinase 3Ξ² (GSK3Ξ²). Moreover, the effect of Chr was further confirmed by EW233, a structural analog of Chr that exhibited an improved pharmacokinetic profile. To further verify the role of Chr and EW233, we utilized our previously established chimeric human cerebral organoid (chCO) model for AD, in which astrogenesis was promoted to mimic the neuron-astrocyte ratio in human brain tissue, and similar dual inhibition of AΞ² and p-tau was also observed. Altogether, our study not only reveals the molecular mechanisms through which dietary flavonoids, such as Chr, mitigate AD pathology, but also suggests that identifying a specific constituent that mimics some of the benefits of these healthy diets could serve as a promising approach to discover new treatments for AD. Show less
The relationship between ambient air pollution and chronic liver disease (CLD), and whether physical activity (PA) modifies this association, remains unclear. We analyzed 17,708 middle-aged and older Show more
The relationship between ambient air pollution and chronic liver disease (CLD), and whether physical activity (PA) modifies this association, remains unclear. We analyzed 17,708 middle-aged and older adults from the 2013 China Health and Retirement Longitudinal Study (CHARLS). Individual-level exposures to CO, O In fully adjusted models, higher pollutant levels were associated with increased CLD risk: CO (OR 1.13, 95% CI 1.04-1.19, pβ=β0.025), O Ambient CO, O Show less
Atherosclerotic cardiovascular disease (ASCVD) is a major threat to human life and health, and dyslipidemia with elevated low-density lipoprotein cholesterol (LDL-C) is an important risk factor, and i Show more
Atherosclerotic cardiovascular disease (ASCVD) is a major threat to human life and health, and dyslipidemia with elevated low-density lipoprotein cholesterol (LDL-C) is an important risk factor, and in the optimal LDL-C scenario, apolipoprotein B (ApoB) has a more predictive value of ASCVD risk. The study is a genome-wide association study (GWAS) based on a European population. A large GWAS dataset for atherosclerotic cardiovascular diseases was targeted, including coronary heart disease (CHD), ischemic stroke (IS), large-artery atherosclerotic stroke (ISL), small-vessel stroke (ISS), and myocardial infarction (MI). Univariate two-sample mendelian randomization (MR) analyses of ApoB and the above cardiovascular diseases were performed separately, and the association was assessed mainly using the inverse variance weighted (IVW) method, with confidence intervals for the superiority ratios set at 95%. In addition, the experiment was supplemented using MR-Egger, weighted model and weighted median (WM). Based on the results of univariate two-sample mendelian randomisation analysis, it was shown that there was a causal relationship between ApoB and CHD (ORβ=β1.710, 95% CI 1.529-1.912, Pβ=β0.010), ISL (ORβ=β1.430, 95% CI 1.231-1.661, Pβ=β2.714E-06), ISS (ORβ=β1.221, 95% CI 1.062-1.405, Pβ=β0.005) were causally related to each other and the disease prevalence ratio was positively correlated with ApoB concentration. This MR analysis demonstrated a causal relationship between ApoB and CHD, ISL, ISS, but not with the risk of developing IS and MI, which further validated the relationship between ApoB and the risk of ASCVD, and contributed to a better understanding of the genetic impact of ApoB on ASCVD, and to a certain extent, could improve the management of ApoB and reduce the prevalence of ASCVD. Show less
Zijun Zhu, Rongxing Wei, Hailong Li+5 more Β· 2025 Β· FASEB journal : official publication of the Federation of American Societies for Experimental Biology Β· added 2026-04-24
Inflammatory bowel disease (IBD) with the two predominant endophenotypes-Crohn's disease (CD) and ulcerative colitis (UC)-represents a group of chronic gastrointestinal inflammatory conditions. Since Show more
Inflammatory bowel disease (IBD) with the two predominant endophenotypes-Crohn's disease (CD) and ulcerative colitis (UC)-represents a group of chronic gastrointestinal inflammatory conditions. Since most genetic associations with IBD are often limited to independent subtypes, we reported a genome-wide association study (GWAS) cross-trait analysis combined with CD and UC to enhance statistical power. Initially, we detected 256 association signals at 54 genomic susceptibility loci and further characterized the functionality of variants within these regions. Subsequently, we revealed tissue and cell-specific heritability enrichment, particularly in whole blood, small intestine terminal ileum, spleen, lung, and colon transverse. Leveraging multi-omics datasets, we adopted a two-pronged approach comprising summary data-based Mendelian randomization (SMR) and transcriptome-wide association study (TWAS) to pinpoint likely causal genes and variants. Further, RNA-seq analysis facilitated the evaluation of differential expression and co-expression in intestinal tissues. Through a multi-stage prioritization strategy, compelling evidence for putative targets was nominated; notably highlighting several potential susceptibility genes such as IL27 and SBNO2. Finally, we utilized Mendelian randomization (MR) analysis with diverse datasets to verify the convergence of these two endophenotype-driven genes. Our investigation yields valuable insights to inform genetic mechanisms in IBD and reveal potential causal gene targets. Show less
Fatty acyl desaturases (Fads) are known to play critical roles in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) in fish species. To date, research on Fads in fish has predomina Show more
Fatty acyl desaturases (Fads) are known to play critical roles in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) in fish species. To date, research on Fads in fish has predominantly focused on Fads2, while studies on Fads1 have been rarely reported. Acipenseriformes, commonly known as Chondrostei, are an ancient fish lineage with unique evolutionary history. However, the biological roles and evolutionary status of Fads1 in Chondrostei remain unclear, which constrains our understanding of the evolutionary processes shaping LC-PUFA biosynthesis in this lineage. In this study, we identified and characterized a fads1 gene from Chinese sturgeon (Acipenser sinensis), a critically endangered Chondrostei, using molecular cloning and multiple bioinformatic analyses. The spatio-temporal expression patterns, functional characteristics, and transcriptional regulation in response to dietary fatty acids were investigated. The coding sequence of the fads1 gene was 1317Β bp in length, encoding a protein of 438 amino acids. Bioinformatic analyses suggested high conservation of fads genes across Chondrostei despite their complex evolutionary history. Functional characterization in yeast showed that Chinese sturgeon Fads1 exhibited Ξ5 desaturation activity, efficiently converting 20:3n-6 to arachidonic acid (ARA) and 20:4n-3 to eicosapentaenoic acid (EPA). Fatty acid composition analysis indicated that Chinese sturgeon could biosynthesize LC-PUFAs when they are deficient in their diets. Taken together, these results suggest that fads1 plays a crucial role in LC-PUFA biosynthesis in Chinese sturgeon, which provides solid theoretical basis for dietary LC-PUFA requirement of Chinese sturgeon. Furthermore, our findings provide novel insights into evolutionary diversification of fads genes in fish species. Show less
Yuemei Zhang, Yuxin Cao, Yongxin Sun+12 more Β· 2025 Β· Proceedings of the National Academy of Sciences of the United States of America Β· National Academy of Sciences Β· added 2026-04-24
The activation of blood monocytes and the infiltration of monocyte-derived macrophages into the vessel walls are the central part of atherosclerosis. However, the mechanisms underlying the processes r Show more
The activation of blood monocytes and the infiltration of monocyte-derived macrophages into the vessel walls are the central part of atherosclerosis. However, the mechanisms underlying the processes remain unclear. Here, we report that G-protein signaling modulator 1 (GPSM1) plays a critical role in atherogenesis. We found that GPSM1 expression in lesional macrophages was increased during atherosclerosis development both in mice and humans. Myeloid-specific GPSM1 ablation protects mice against atherosclerosis and reduces aortic inflammation in both Show less
To investigate the impact of obesity on brain structure and cognition using large neuroimaging and genetic data. Associations between body mass index (BMI), gray matter volume (GMV), whiter matter hyp Show more
To investigate the impact of obesity on brain structure and cognition using large neuroimaging and genetic data. Associations between body mass index (BMI), gray matter volume (GMV), whiter matter hyper-intensities (WMH), and fluid intelligence score (FIS) were estimated in 30283 participants from the UK Biobank. Longitudinal data analysis was conducted. Genome-wide association studies were applied to explore the genetic loci associations among BMI, GMV, WMH, and FIS. Mendelian Randomization analyses were applied to further estimate the effects of obesity on changes in the brain and cognition. The observational analysis revealed that BMI was negatively associated with GMV (rβ―=β―-0.15, pβ―<β―1 The phenotypic and genetic association between obesity and aging brain and cognitive decline suggested that weight control could be a promising strategy for slowing the aging brain. Show less
Childhood cancer can disrupt family functioning, increase caregiver psychological distress, and impair caregiver quality of life. While family resilience is crucial for adaptation, most research has f Show more
Childhood cancer can disrupt family functioning, increase caregiver psychological distress, and impair caregiver quality of life. While family resilience is crucial for adaptation, most research has focused on individual-level factors, neglecting heterogeneity and multilevel influences on family resilience. Guided by the Social Ecological Model (SEM), this cross-sectional observational study used latent profile analysis (LPA) to identify distinct profiles of family resilience among caregivers of children with cancer and to explore factors associated with these profiles. Between July 2022 and March 2024, 292 caregivers were recruited. Family resilience was measured using the Family Resilience Assessment Scale. LPA was employed to identify resilience profiles, and binary logistic regression was used to explore influencing factors. Two latent profiles were identified: the Low Resources-Low Positivity profile (86%) and the High Internal Resilience profile (14%). The Low Resource-Low Positivity profile demonstrated generally lower scores, especially in utilizing social and economic resources and maintaining a positive outlook. The High Internal Resilience profile showed higher scores across all family resilience dimensions, particularly in communication/problem solving, positive outlook, and meaning-making, while the use of external social and economic resources remained relatively lower. Univariate analysis showed significant differences between profiles in residence, number of siblings, caregiver education, individual resilience, social support, caregivers' physical and psychological well-being and child communication (caregiver-reported). Binary logistic regression identified having more than one child (ORβ=β3.184, 95% CI: 1.437β~β7.057, Pβ=β0.004) and higher individual resilience (ORβ=β1.095, 95% CI: 1.028β~β1.165, Pβ=β0.005) as significant predictors of High Internal Resilience profile. This study identified two distinct family resilience profiles among caregivers of children with cancer. Limited use of social and economic resources was common, while caregiver resilience and having multiple children predicted higher family resilience. Interventions should enhance caregiver coping capacity, support one-child families through peer and family programs, and improve access to social support, flexible employment, and affordable care to strengthen family resilience. Not applicable. Show less
Early identification of individuals at risk for cognitive impairment is essential for timely intervention and public health planning. While sociodemographic and clinical predictors are well recognized Show more
Early identification of individuals at risk for cognitive impairment is essential for timely intervention and public health planning. While sociodemographic and clinical predictors are well recognized, the role of nutrition and its interactions in cognitive health remains less explored. Using data from the 2011-2014 National Health and Nutrition Examination Survey (NHANES, Ensemble models demonstrated excellent predictive performance, consistently outperforming traditional classifiers. Key predictors included education, age, socioeconomic status, and chronic disease conditions. Among nutritional factors, vitamin B2 emerged as consistently associated with lower predicted cognitive impairment risk across all three models, with notable interactions observed with copper and vitamin E. Exploratory Interpretable machine learning models integrating cognitive tests with demographic, clinical, and nutritional variables can accurately predict cognitive impairment. Nutritional predictors, particularly vitamin B2 and its interactions, may contribute to model performance and biological plausibility, suggesting potential avenues for stratified monitoring strategies. Show less
Relying on a single biomarker in biomedical analysis is often insufficient for accurate disease or pathogen determination. A recent trend is using simultaneous multiplex detection of multiple biomarke Show more
Relying on a single biomarker in biomedical analysis is often insufficient for accurate disease or pathogen determination. A recent trend is using simultaneous multiplex detection of multiple biomarkers to improve diagnostic accuracy and throughput. To enable multiplex detection, we developed a series of surface-enhanced Raman scattering (SERS) nanoprobes, referred to as nanoaggregate-embedded beads (NAEBs). These NAEBs were synthesized using three distinct Raman reporter molecules: Safranin O, ethyl violet, and cresyl violet acetate. By integrating the NAEBs with magnetic nanoparticles and a simple capillary magnetofluidic device, we developed a rapid and simultaneous multiplex detection platform for genetic analysis of an aquacultural pathogen Vibrio parahaemolyticus (VP) for pirA, pirB, and ompA and genotyping of Alzheimer's disease's risk factor biomarker Apoliproprotein E (ApoE). For VP detection, a limit of detection (LOD) as low as ~β10 Show less
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia and insulin resistance, Migraine is a common chronic neurological disease caused by increased excitability of the Show more
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia and insulin resistance, Migraine is a common chronic neurological disease caused by increased excitability of the central nervous system, both exerting substantial health burdens. However, the shared genetic basis and underlying molecular mechanisms remain largely unexplored. This study integrates single-cell data and Mendelian randomization (MR) analysis to identify comorbidity-associated genes and elucidate potential mechanistic links between these two conditions. Single-cell datasets from T2DM and migraine were analyzed to identify differentially expressed genes (DEGs). MR analysis was employed to prioritize key causal genes, followed by network-based functional characterization, disease-drug association analysis, cell annotation, and pseudo-time trajectory modeling. Analysis of single-cell data identified 2,128 migraine-associated and 3,833 T2DM-associated genes, with 714 genes shared between the two diseases. MR analysis highlighted AP4E1 and HSD17B12 as key regulators implicated in both conditions. Network analysis further linked these genes to lipid metabolism and vesicle transport pathways. Computational predictions revealed common comorbidities, including metabolic dysregulation and chemical-induced liver injury, as well as potential therapeutic agents such as valproic acid and bisphenol A. Single-cell annotation identified six major immune cell types in T2DM (T cells, NK cells, B cells, CD14 monocytes, CD16 monocytes, and dendritic cells), with T cells emerging as central players. In migraine, five immune cell types were identified (CD4 T cells, CD8 T cells, B cells, NK cells, and monocytes), with monocytes being the predominant cell type. Pseudo-time analysis delineated seven subpopulations of T cells and four subpopulations of monocytes, suggesting distinct functional trajectories in disease pathogenesis. However, due to the use of peripheral blood-derived single-cell data, genes primarily expressed in the central nervous system, such as CALCA and RAMP1, could not be detected, limiting the identification of certain migraine-specific pathways. This single-cell data and MR analysis investigation identifies AP4E1 and HSD17B12 as pivotal genetic determinants in T2DM-migraine comorbidity, shedding light on their molecular interplay and potential therapeutic relevance. Show less
Sijie Gu, Haoran Feng, Xiaomei Li+10 more Β· 2025 Β· Molecular therapy : the journal of the American Society of Gene Therapy Β· Elsevier Β· added 2026-04-24
Preventing the progression from acute kidney injury (AKI) to chronic kidney disease (CKD) remains a considerable clinical challenge. In this study, we elucidate the role of WNT5A in accelerating the A Show more
Preventing the progression from acute kidney injury (AKI) to chronic kidney disease (CKD) remains a considerable clinical challenge. In this study, we elucidate the role of WNT5A in accelerating the AKI-to-CKD transition and its underlying mechanisms. Renal biopsies from patients with AKI showed marked upregulation of WNT5A and its receptor, CD146, in proximal tubules, with higher expression in patients with CKD progression. In murine AKI models, Wnt5a knockdown attenuated CKD progression. Conversely, proximal tubular overexpression of Wnt5a exacerbated renal fibrosis in ischemia-reperfusion injury (IRI) mice, which was alleviated by Box5, a specific WNT5A antagonist. In vitro, WNT5A overexpression in transforming growth factor Ξ² (TGF-Ξ²)-stimulated HK-2 cells promoted CD146 upregulation, activated JNK phosphorylation, and enhanced SNAI1 expression. The genetic silencing of WNT5A/CD146 and JNK inhibition suppresses SNAI1 expression and attenuates fibrotic responses. Mechanistically, JNK-mediated c-JUN phosphorylation promoted its interaction with KLF5 at the SNAI1 promoter, driving renal fibrosis. Elevated serum levels of soluble CD146 correlated with renal function in patients with AKI and were higher in patients exhibiting CKD progression. Inhibition of WNT5A could serve as a therapeutic target for delaying renal fibrosis in AKI progression. Show less
Breast cancer (BC) is the most prevalent malignancy among women worldwide. Growing evidence highlights the crucial role of circular RNAs (circRNAs) in BC carcinogenesis; however, their underlying mech Show more
Breast cancer (BC) is the most prevalent malignancy among women worldwide. Growing evidence highlights the crucial role of circular RNAs (circRNAs) in BC carcinogenesis; however, their underlying mechanisms remain largely unknown. In this study, we identify circCLASP1, which is significantly upregulated in BC tissues (nβ=β65) and serum samples (nβ=β61). Its expression correlates with lymph node metastasis, ki67 expression, and tumor size. Receiver operation characteristic (ROC) curve analysis reveals area under the curve (AUC) values of 0.8196 (BC tissues) and 0.8902 (BC serum), respectively. Functionally, circCLASP1 knockdown significantly suppresses BC cell proliferation, migration, and invasion. Mechanistically, circCLASP1 prevents the ubiquitin-mediated degradation of GLI1 protein by facilitating its interaction with CCT2, thereby stabilizing GLI1. Moreover, circCLASP1 enhances the nuclear accumulation of GLI1, leading to increased SNAIL expression and thereby upregulating the expression of CCL2 and CCL5, which in turn promotes macrophage M2 polarization, ultimately resulting in BC progression and subsequent lung metastasis. Further analysis reveals that U2AF2 regulates circCLASP1 biogenesis. Collectively, these findings demonstrate that circCLASP1 promotes BC progression and an immunosuppressive microenvironment via the CCT2/GLI1/SNAIL axis, highlighting its potential as a prognostic biomarker and therapeutic target for BC. Show less
Biomolecular condensates, membrane-less assemblies formed by phase separation, are implicated in neurodegenerative disease, but their role in Alzheimer's disease (AD) remains unclear. Here, we report Show more
Biomolecular condensates, membrane-less assemblies formed by phase separation, are implicated in neurodegenerative disease, but their role in Alzheimer's disease (AD) remains unclear. Here, we report that in the brain of AD patients and animal models, an elevation of poly(C)-binding protein 2 (PCBP2) correlates with biomolecular condensation that involves phase separation. These condensates sequester large numbers of mitochondrial and mRNA-binding proteins, leading to the outside impairment of mitochondrial morphology and function, and BACE1 mRNA decay relative to amyloid deposition. We then identify a small molecule CN-0928 that inhibits the condensates by reducing PCBP2 protein level and mitigates AD pathology and cognitive decline, in which CN-0928 binding to a target protein integrator complex subunit 1 (INTS1) allows to regulate PCBP2 expression. Our findings place PCBP2 condensates as a key player that cooperates the seemingly disparate but important pathways, and show pharmacological modulation of PCBP2 as an effective approach for treating AD. Show less
NRBF2, a component of autophagy-associated PIK3C3/VPS34-containing phosphatidylinositol 3-kinase complex, plays a crucial role in learning and memory processes, yet its specific impact on memory and t Show more
NRBF2, a component of autophagy-associated PIK3C3/VPS34-containing phosphatidylinositol 3-kinase complex, plays a crucial role in learning and memory processes, yet its specific impact on memory and the underlying molecular mechanisms remains unclear. Here, we utilized NRBF2 knockout mice to examine its influence on the time course of fear memory. Employing quantitative PCR, Western blot analysis, behavioral tests, and electrophysiology, we investigated the mechanisms through which NRBF2 affects memory processing. We observed an increase in This study offer new insights into the role of NRBF2 and highlight the potential of targeting NRBF2 as a therapeutic strategy for addressing cognitive deficits associated with various disorders. Show less
Dyslipidemia is linked to pregnancy complications, but its causal role remains uncertain. This two-sample Mendelian Randomization (MR) study investigated the causal relationship between lipid traits a Show more
Dyslipidemia is linked to pregnancy complications, but its causal role remains uncertain. This two-sample Mendelian Randomization (MR) study investigated the causal relationship between lipid traits and pregnancy complications and evaluated the impact of lipid-modifying drug targets. Genetic instruments for lipid traits and targets for lipid-modifying drugs were obtained from the Global Lipids Genetics Consortium. Three pregnancy complications' summary statistics came from the FinnGen R9 database. Significant drug targets underwent further analysis using Expression Quantitative Trait Loci data, and mediation analysis identified potential mediators. Increased high-density lipoprotein cholesterol (HDL-C) reduced the incidence of preeclampsia (OR: 0.755, 95% CI: 0.639-0.891, p=0.001, FDR=0.012) and gestational diabetes mellitus (GDM) (OR: 0.835, 95% CI: 0.741-0.942, p=0.003, FDR=0.018). Genetic proxies for cholesteryl ester transfer protein ( Elevated HDL-C levels help prevent preeclampsia and GDM. Show less
The treatment and prognosis of cardiac amyloidosis (CA) depend heavily on the accurate identification of amyloid protein types. Histopathological methods are the most commonly used approach, but often Show more
The treatment and prognosis of cardiac amyloidosis (CA) depend heavily on the accurate identification of amyloid protein types. Histopathological methods are the most commonly used approach, but often produce inconclusive results. The application of mass spectrometry with laser microdissection mass spectrometry based on non-targeted proteomics in CA diagnosis is gradually being recognized, but it is expensive, time-consuming, and still in the early stages of scientific research applications. This study aims to establish a novel typing method based on targeted semi-quantitative proteomics to address the shortcomings of existing methods. Formalin-fixed, paraffin-embedded (FFPE) myocardial tissue samples from 52 CA and 52 hypertrophic cardiomyopathy (HCM) patients were analyzed. A semi-quantitative typing method was developed using triple quadrupole mass spectrometry, with laser microdissection mass spectrometry (LMD-MS) serving as the reference standard. A total of 52 peptides were analyzed. Key amyloid-associated proteins (AAPs) -apolipoprotein A-IV (apo A-IV), apolipoprotein E (apo E), and serum amyloid P component (SAP) - showed high diagnostic accuracy, with AUC values of 0.964, 0.999, and 0.923, respectively. Transthyretin (TTR), immunoglobulin light chains- ΞΊ (IGL - ΞΊ), and IGL-Ξ» were semi-quantified using normalized scores (NS) adjusted for microdissection and peptide peak areas. An NS This targeted semi-quantitative mass spectrometry method has high consistency with non-targeted LMD-MS typing, with an accuracy higher than IHC (100Β % vs. 30.8Β %), while compensating for the shortcomings of non-targeted proteomics. It provides a practical method for CA typing in routine clinical laboratories and may help identify rare subtypes of amyloidosis in the future. Show less
The study aimed to characterise presenteeism among nurses and identify nurses' presenteeism associated with distinct latent profiles. This study employed a cross-sectional descriptive approach. From J Show more
The study aimed to characterise presenteeism among nurses and identify nurses' presenteeism associated with distinct latent profiles. This study employed a cross-sectional descriptive approach. From July to December 2024, data were collected from 404 Chinese clinical nurses across four tertiary hospitals in Sichuan Province, Southwest China, using demographic questionnaires, the Stanford Presenteeism Scale (SPS-6), and the Challenge- and Hindrance-Related Self-Reported Stress Scale (C-HSS). A latent profile analysis was conducted on SPS-6 scores using Mplus 8.3, followed by univariate analyses to compare characteristics across subgroups. The total mean score of nurses' presenteeism is (16.13βΒ±β4.46), with approximately 59.4% classified as having a high level of presenteeism. Four latent profiles of nurses' presenteeism were identified through LPA: low fatigue-low work constraint (19.8%), low fatigue-high work constraint (33.9%), high fatigue-low work constraint (18.8%), and high fatigue-high work constraint (27.5%). Nurses demonstrated moderately severe presenteeism, with LPA revealing four distinct phenotypes characterised by divergent fatigue- work constraint configurations. This heterogeneity underscores the need for stratified interventions addressing unique risk profiles across subgroups. Administrators should adopt targeted interventions according to the characteristics of nurses in different profiles to minimise nurses' loss of productivity. This study addresses the evidence gap regarding the significant heterogeneity of presenteeism among nurses and the lack of precise identification, and identifies four distinct latent profiles of presenteeism. The findings provide critical evidence for nursing managers to design and implement differentiated intervention strategies tailored to groups with different risk characteristics. The study followed the STROBE guideline. This study did not include patient or public involvement in its design, conduct or reporting. Show less
To establish the reference interval for the serum lipid index in pregnant women and to explore the relationship between lipid metabolism levels and pregnancy outcomes. Data were derived from 446 pregn Show more
To establish the reference interval for the serum lipid index in pregnant women and to explore the relationship between lipid metabolism levels and pregnancy outcomes. Data were derived from 446 pregnancy women and 317 healthy non-pregnant women. Serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein (a) [Lp(a)], and hypersensitive C-reactive protein (hs-CRP) were measured in both groups. The mean and standard deviation of each index were calculated to establish the reference range of normal serum lipid levels in pregnant women in mid-to-late pregnancy. The associations between serum lipid levels and perinatal outcomes were assessed statistically. There were no significant differences in age, pregnancy, or parity between the adverse outcome and normal delivery groups, but the caesarean section rate was significantly higher in the adverse outcome group. The levels of hs-CRP, TG, TC, HDL-C, LDL-C, and ApoA1 were significantly higher in the adverse outcome group. Elevated hs-CRP, TG, and HDL-C levels were risk factors for adverse pregnancy outcomes. According to the receiver operating characteristic curve, the optimal threshold of the combined diagnosis of these three indicators to predict adverse pregnancy outcomes was 0.534, and the area under the curve was 0.822. The establishment of lipid reference intervals in the second and third trimesters of pregnancy can effectively evaluate lipid metabolism in pregnant women, and the measurement of lipid metabolism in pregnant women is helpful in predicting adverse pregnancy outcomes. Show less
Hepatic VLDL overproduction, tightly modulated by insulin signaling, plays a pivotal role in the progression of atherosclerosis (AS). The present study aimed to investigate whether inhibition of hepat Show more
Hepatic VLDL overproduction, tightly modulated by insulin signaling, plays a pivotal role in the progression of atherosclerosis (AS). The present study aimed to investigate whether inhibition of hepatic VLDL overproduction is a novel therapeutic strategy for the homogeneous tea polysaccharide (TPS3A) to ameliorate AS under insulin resistance (IR) conditions and the potential molecular basis involved. Results showed that TPS3A supplementation effectively alleviated systemic IR and delayed atherosclerotic plaque progression in HFD-exposed ApoE Show less